At the University of Kentucky (UK), we have established the Center for Clinical and Translational Science (CCTS) as a home for clinical and translational research. UK is located in Lexington, on the western edge of mid-Appalachia, one of the poorest areas of the country, where there are unprecedented disparities in disease and mortality. Many of these disparities stem from risky behaviors, such as smoking, drug abuse, and obesity. In this proposal, our overarching goal is to transform the pace, effectiveness, and quality of translational research at UK which will result in better health for the people of mid-Appalachia. Scientific discovery offers the potential for improved care, with community-based research offering a faster impact on health through a better dissemination of optimal medical care. However, scientific discoveries often do not reach the community due to the many difficulties with navigating the complex process of clinical and translational research. In this application, we will capitalize on our strengths in education, basic and clinical sciences, as well as our outstanding programs in practice- and community- based participatory research. These efforts will result in scientific discovery that will impact the health of the Appalachian rural community in the near term, and prime the pipeline for the future. To accomplish these goals, UK will form a collaboration with Marshall University, which is 2 hr away in Huntington, WV. In addition, we will form an Appalachian Translational Reseach Network involving not only Marshall, but also the CTSAs at the Ohio State University, University of Cinncinati, Morehead University, and Pikeville School of Osteopathic Medicine. This network will be especially important in the further development of our strong programs in community based participatory research. To help integrate our efforts, we have developed an innovative group of faculty CATalysts, who will build collaborative team science programs backed by generous pilot funding that will target novel ideas at all levels of science. New CCTS programs in Drug Development, 'Novel Methodologies, and Risk-Related Behavior Research will capitalize on our strengths, engage investigators with diverse areas of expertise, and will more quickly impact the health of the Appalachian community. We have recently recruited a new leader in Biomedical Informatics and have invested heavily in this program, which will greatly improve our ability to transform data into knowledge throughout the CCTS. Through these initiatives, UK will fulfill its mandate as Kentucky's flagship university to improve the health of Central Appalachia, and thereby add unique value to improvements in the health of the nation.